Astex Pharmaceuticals, 436 Cambridge Science Park, Cambridge, UK.
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK.
Nat Commun. 2022 Apr 27;13(1):2270. doi: 10.1038/s41467-022-30017-z.
There is growing evidence for the importance of 3' untranslated region (3'UTR) dependent regulatory processes. However, our current human 3'UTR catalogue is incomplete. Here, we develop a machine learning-based framework, leveraging both genomic and tissue-specific transcriptomic features to predict previously unannotated 3'UTRs. We identify unannotated 3'UTRs associated with 1,563 genes across 39 human tissues, with the greatest abundance found in the brain. These unannotated 3'UTRs are significantly enriched for RNA binding protein (RBP) motifs and exhibit high human lineage-specificity. We find that brain-specific unannotated 3'UTRs are enriched for the binding motifs of important neuronal RBPs such as TARDBP and RBFOX1, and their associated genes are involved in synaptic function. Our data is shared through an online resource F3UTER ( https://astx.shinyapps.io/F3UTER/ ). Overall, our data improves 3'UTR annotation and provides additional insights into the mRNA-RBP interactome in the human brain, with implications for our understanding of neurological and neurodevelopmental diseases.
越来越多的证据表明 3'非翻译区（3'UTR）依赖的调控过程很重要。然而，我们目前的人类 3'UTR 目录并不完整。在这里，我们开发了一个基于机器学习的框架，利用基因组和组织特异性转录组特征来预测以前未注释的 3'UTRs。我们在 39 个人类组织中确定了与 1563 个基因相关的未注释的 3'UTRs，其中在大脑中发现的丰度最大。这些未注释的 3'UTRs 显著富集 RNA 结合蛋白（RBP）基序，并且表现出高度的人类谱系特异性。我们发现，大脑特异性的未注释的 3'UTRs 富含重要神经元 RBP（如 TARDBP 和 RBFOX1）的结合基序，其相关基因参与突触功能。我们的数据通过在线资源 F3UTER（https://astx.shinyapps.io/F3UTER/）共享。总的来说，我们的数据提高了 3'UTR 的注释，并为人类大脑中的 mRNA-RBP 相互作用组提供了更多的见解，这对我们理解神经和神经发育疾病具有重要意义。
